Presentation of HER2 epitopes using a filamentous plant virus-based vaccination platform

Abstract

Human epidermal growth factor receptor 2 (HER2)-positive cancers are aggressive, have poor prognoses, and have a high rate of metastasis and relapse. Immunotherapy (e.g. trastuzumab) has shown improvement in the outcome for HER2 patients. Development of drug resistance and short half-lives limiting the duration of the therapy are barriers in the development of effective therapeutic strategies. Furthermore, while passive immunotherapy provides treatment, it does not reduce the risk of recurrence of the disease. These barriers have fueled the development of active immunotherapies using HER2 vaccines. We turned toward the development of a nanoparticle-based peptide vaccine. Specifically, we integrated HER2 epitopes on the plant-produced vaccination platform potato virus X (PVX) to overcome immunological tolerance against HER2. The carrier acts as an adjuvant and improves stability and B cell presentation of the epitopes. Immunizations of FVB/N mice resulted in the production of HER2-specific antibodies, as shown by ELISA and confocal microscopy using HER2-positive human cancer cell lines.